Adaptive regulation maintains posttetanic potentiation at cerebellar granule cell synapses in the absence of calcium-dependent PKC.

ABSTRACT

Posttetanic potentiation (PTP) is a transient, calcium-dependent increase in the efficacy of synaptic transmission following elevated presynaptic activity. The calcium-dependent protein kinase C (PKC(Ca)) isoforms PKCα and PKCß mediate PTP at the calyx of Held synapse, with PKCß contributing significantly more than PKCα. It is not known whether PKC(Ca) isoforms play a conserved role in PTP at other synapses. We examined this question at the parallel fiber → Purkinje cell (PF→PC) synapse, where PKC inhibitors suppress PTP. We found that PTP is preserved when single PKC(Ca) isoforms are knocked out and in PKCα/ß double knock-out (dko) mice, even though in the latter all PKC(Ca) isoforms are eliminated from granule cells. However, in contrast to wild-type and single knock-out animals, PTP in PKCα/ß dko animals is not suppressed by PKC inhibitors. These results indicate that PKC(Ca) isoforms mediate PTP at the PF→PC synapse in wild-type and single knock-out animals. However, unlike the calyx of Held, at the PF→PC synapse either PKCα or PKCß alone is sufficient to mediate PTP, and if both isoforms are eliminated a compensatory PKC-independent mechanism preserves the plasticity. These results suggest that a feedback mechanism allows granule cells to maintain the normal properties of short-term synaptic plasticity even when the mechanism that mediates PTP in wild-type mice is eliminated.